PREDISPOSITION OF WOLFRAM-SYNDROME HETEROZYGOTES TO PSYCHIATRIC-ILLNESS

Identification of specific genes that predispose to psychiatric illnes s will lead to more precise psychiatric diagnosis and more effective t reatment. Heterozygous carriers of genes for many autosomal recessive syndromes may be 1% or more of the general population. Thus, if mutati ons at a specific locus produce psychiatric manifestations in homozygo us affected individuals, it is important to determine whether mutation s at such a locus also predispose heterozygous carriers to psychiatric disorders. The hypothesis that heterozygous carriers of the gene for the Wolf ram syndrome (WS) are predisposed to psychiatric illness was supported previously by the finding of an excess of psychiatric hospit alizations and suicides in WS blood relatives compared to spouse contr ols.(1) This hypothesis has now been tested further by comparing the n umber of psychiatrically hospitalized blood relatives with the specifi c marker haplotype associated with the Wolf ram syndrome gene in their families to the number expected under the null hypothesis, calculated from Mendelian inheritance principles and the estimated haplotype fre quency.(2) The proportion of psychiatrically hospitalized relatives wh o were WS carriers (10/11) was much higher than expected (3.1/11), lea ding to the provisional estimate that WS gene carriers are 26-fold mor e likely to require psychiatric hospitalization than non-carriers.